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Biomedical subjects

R M Thompson

Publications and source records attributed to R M Thompson.

At least 19 recordsLinked to original sources

Differential induction of indoleamine-2,3-dioxygenase (IDO) by interferon-gamma in human gynecologic cancer cells.

Induction of indoleamine-2,3-dioxygenase (IDO) by interferon-gamma (IFN-gamma) is thought to be one mechanism underlying IFN-gamma's antineoplastic properties. Since clinical trials with IFN-gamma have yielded variable efficacy in treating cancers of gynecological origin, we tested the effects of IFN-gamma on cell growth and IDO activity in cell lines from seven gynecologic and five breast cancers. At a dose of 250 IU/ml, IFN-gamma suppressed cell growth and induced IDO activity in one cervical (C41), one vulva (A431), one breast (HS578T) and two ovarian (OVCAR-3, CAOV-3) cancer cell lines. Differing inhibition of cell growth, but with no induction of IDO activity, was found with IFN-gamma treatment of the other cell lines.

Biomarkers, Tumor

Angiosarcoma after tylectomy and radiation therapy for carcinoma of the breast.

BACKGROUND: Angiosarcoma (AS) is an uncommon tumor that rarely develops after external beam radiation therapy (EBRT). Thirty-six cases have been reported in the literature. METHODS: The authors present two additional cases. Each of these patients received breast-conserving treatment for breast carcinoma that consisted of tylectomy and EBRT. In each case, AS developed in the field of prior irradiation. RESULTS: Currently, seven cases of AS after radiation therapy for breast-conserving treatment of breast carcinoma have been reported. The average time interval between the administration of radiation therapy and the development of AS is 8.6 years. CONCLUSIONS: This complication is rare and should not influence the decision to offer breast-conserving therapy to patients. However, patients should be informed that AS may develop as a result of radiation therapy.

Aged

Increased neopterin levels in brains of patients with human immunodeficiency virus type 1 infection.

Postmortem levels of native neopterin (D-erythro-neopterin) were measured in cerebral cortical samples from 44 human immunodeficiency virus type 1-infected and eight uninfected, nonneurological control patients. Cerebral cortical gray and white matter neopterin levels for the controls ranged from 0.5 to 7.2 pmol/mg of protein in contrast to neopterin levels in brains of the virus-infected patients, which frequently were more than threefold and occasionally more than 30-fold higher than mean control levels. Cortical neopterin levels did not correlate with severity of the acquired immunodeficiency syndrome dementia complex, but subcortical levels correlated with the presence of active human immunodeficiency virus type 1 infection, as reflected by pathological evidence of multinucleated giant cell encephalitis. Evidence of opportunistic cytomegalovirus infections in approximately 25% of the human immunodeficiency virus type 1-infected patients was associated with enhanced levels of neopterin in frontal cortex.

Acquired Immunodeficiency Syndrome

A rostral-caudal concentration gradient in cerebrospinal fluid adrenocorticotropin.

In two separate experiments, cerebrospinal fluid (CSF) adrenocorticotropin immunoreactive (ACTH-IR) concentrations in the rhesus monkey followed a significant rostral-caudal gradient. In the first study, CSF was sampled from an indwelling catheter in awake animals. The mean ACTH-IR concentration in the cisternal region was 12.3 pg/ml, as compared to 8.56 pg/ml in the lumbar region. In the second study, CSF was sampled in a different group of monkeys by percutaneous puncture at the cisterna magna and at L5-L6. In this study, the mean ACTH-IR concentration in samples collected from the cistern was also greater than the concentration from L5-L6. In addition, a significant correlation within subjects was found between samples collected from the two sites (r = 0.86). These results demonstrate that the site of CSF sampling is a variable in determining CSF ACTH-IR concentrations and suggest that lumbar CSF ACTH-IR concentrations in humans may be interpreted as indexes of ACTH changes at higher levels in the central nervous system.

Adrenocorticotropic Hormone

Mass spectrometry of some ultraviolet absorbing derivatives of sugars and related alditols: identification in biologic fluids after separation by high performance liquid chromatography.

The 70 eV electron impact mass spectra of the acyclic perbenzoyl 0-benzyloximes of several mono- and disaccharides of clinical interest and the perbenzoates of certain related alditols have been obtained and compared with those of other similar derivatives studied previously. In general, the spectra of the benzyloximes contain molecular ions and characteristic fragments due to [C6H5]+,[C7H7]+,[C6H5CO]+ and [C6H5CooH]+., losses of HCHO, C6H5COO. and C6H5COOH, and cleavages along the carbon chain. The most unique ions in these spectra arise from the combined loss of C7H7. and C6H5COO.from the molecular ion: m/z 191 (C3), m/z 339 (deoxy-C5), m/z 459 (C5), m/z 473 (deoxy-C6), and m/z 593 (C6). The alditol benzoates fragment similarly, but they do not yield molecular ions. These data are being used to help confirm the identities of carbohydrates in biologic fluids fractionation by high performance liquid chromatography, prior to the establishment of routine quantitative assays for several of these compounds.

Benzoates

Does the conventional cystogram exaggerate reflux?

We studied 35 patients with anterograde and retrograde cystography. Many patients who had reflux on retrograde cystography either did not have reflux or the reflux was reduced significantly on anterograde cystography. Furthermore, when reflux was seen on anterograde cystography it appeared to have more prognostic value than when seen on retrograde cystography. The question is raised of whether much reflex seen on retrograde cystography is not actually an artifact of the examination and does not exist beyond circumstances of the test.

Adolescent

Evidence for the epoxide-diol pathway in the biotransformation of mephenytoin.

A dihydrodiol metabolite of mephenytoin (5-dihydroxycyclohexadienyl)-5-ethyl-3-methylhydantoin and other mono- and dihydroxylated and N-demethylated metabolites were identified in urine from a male epileptic patient receiving therapy with mephenytoin (300 mg/day). Metabolites, extracted from urine before and after enzymatic hydrolysis, were derivatized with a trimethylsilyl reagent and analyzed by combined gas chromatography and mass spectrometry. Two previously unreported metabolites were characterized: 5-ethyl-5-(di-hydroxyphenyl)-3-methylhydantoin and 5-ethyl-5-(hydroxy-methoxy-phenyl)-3-methylhydantoin. The structures of several other metabolites were confirmed: N-demethylmephenytoin, 5-ethyl-5-hydroxyphenylhydantoin, 5-ethyl-5-hydroxyphenyl-3-methylhydantoin and mephenytoin dihyrodiol. The dihydrodiol metabolite was of special interest since it was probably produced via an epoxide intermediate, 5-(epoxy-cyclohexadienyl)-5-ethyl-3-methylhydantoin. Previous reports have demonstrated that epoxides of this structural class are extremely reactive compounds, capable of alkylating biologic macromolecules. Covalent binding of the mephenytoin epoxide to macromolecules may be an important factor in the production of adverse and sometimes fatal side effects observed in patients receiving long-term therapy with mephenytoin.

Adult

Analysis of mono- and disaccharides by high-performance liquid chromatography of the benzyloxime-perbenzoyl derivatives.

A group of biologically important mono- and disaccharides are separated by high-performance liquid chromatography of the benzyloxime-perbenzoyl derivatives on a normal-phase microparticulate column with a hexane-dioxane mixture as the eluting solvent. A single, quantifiable derivative of each sugar is formed easily. These derivatives are detected by UV absorption at either 230 or 254 nm, with a sensitivity in the picomole range at the former wavelength. The sugars in the residues from the evaporation of small aliquots of biologic fluids (10-100 microliter) are derivatized without prior isolation and are determined quantitatively by the use of appropriate internal standards. The analyses could be performed routinely with a simple, inexpensive instrument.

Benzoates

Determination of disaccharides in feces by permethylation and gas chromatography: rapid screening for carbohydrate intolerance in children.

Disaccharides can be identified and determined quantitatively in fecal specimens by permethylation of the components in crude supernatants followed by isothermal gas chromatographic separation on OV-17 columns. The method provides a rapid screening procedure for detecting patients suspected of having a carbohydrate intolerance secondary to intestinal disaccharidase deficiency.

Carbohydrate Metabolism, Inborn Errors

Mass spectrometry of some permethylated apiosyl nucleosides.

The mass spectra of the permethyl derivatives of a group of synthetic D-apio-L-furanosyl nucleosides were collected and compared with those of their ribosyl analogs. While most of the m/e values are the same between analogous spectra, some of the relative intensities differ markedly. Each spectrum contains characteristics ions which are probably due to fragmentation of the dissimilar sugar moieties.

Mass Spectrometry

Identification of drugs, drug metabolites, and other compounds in urine by permethylation and gas-phase analysis.

A small aliquot of urine (50-200 mul) is evaporated to dryness, the residue permethylated with the methylsulfinylmethide carbanion and methyl iodide, and the product mixture separated and analyzed by GC and GC-MS. Certain drugs (especially the anticonvulsants), drug metabolites, mono-, di-, and trisaccharides, and organic acids, including fatty acids and glucuronides, can be identified in the mixture. The technique is probably useful mainly as a screening method for the detection of any of these types of compounds in urine.

Adolescent

Separation of permethylated isomeric glucuronides by gas chromatography and analysis of the mass spectra.

Glucuronic acid conjugates of several foreign compounds (1- and 2-naphthols, 2-, 3-, and 4-hydroxybiphenyls, m- and p-hydroxyphenylphenylhydantoins) were produced in the isolated perfused rat liver and identified in the bile as the permethyl derivatives. Permethylated glucuronide isomers were easily separated by gas chromatography on SE-30 and OV-17 columns. The mass spectra of permethylated glucuronide isomers were very similar. Gas chromatography proved to be most useful for the separation and identification of isomeric glucuronides.

Animals

Permethylation of barbiturates: variation in product ratios with varying methylsulfinylmethide carbanion.

Permethylation of a barbiturate with the methylsulfinylmethide carbanion and methyl iodide gave three products clearly separable by GLC. Alteration of the reaction conditions by varying the barbiturate to carbanion ratio or the barbiturate to carbanion exposure time resulted in a single product for only one examined barbiturate, secobarbital. This derivatization technique is useful for the GLC analysis of polar barbiturate metabolites, such as glucuronides, in biological fluids but is of limited value for the analysis of the parent compounds.

Barbiturates